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BackgroundsThe aim of the current study was to develop a distinctive nanolipid formulation, namely, nanostructured lipid carrier (NLC), which would deliver an antibacterial medication such as mupirocin (MP). Additionally, cinnamon essential oil (CEO), which is reported to exhibit antibacterial activity, was utilized in the development process in an attempt to improve the influence of MP.MethodsAs a consequence, different MP–NLC formulations were developed using the central composite design (CCD) approach. One optimized formula was selected and incorporated within the pre-formulated gel matrix, providing the MP–NLC-gel formula for efficient topical application. MP–NLC-gel was assessed for its physical characteristics to check its suitability for topical application and evaluated for its in vitro drug release over 6 h. Furthermore, it studied the formulation for its stability at different conditions; 25°C ± 2°C and at 4°C ± 3°C for 6 months. Finally, the formulation was examined for its antibacterial performance against gram-positive and -negative bacteria.ResultsThe developed topical NLC-gel formulation demonstrated pH 5.8, viscosity 14,510 cP, and spreadability 58.1 mm, which were seemed to be satisfactory properties for successful topical application. The drug was released successfully for over 6 h with 52.9%. Additionally, it was stable in both storage conditions for 6 months since it displayed non-significant variations in its evaluated characteristics compared to those of fresh preparation. Ultimately, the developed gel formulation could inhibit the growth of different bacterial strains, especially gram-negative strains.ConclusionTo sum up, these findings would demonstrate the efficiency of NLC prepared with CEO and incorporating MP to be a promising antibacterial lipid nanocarrier.

The rise of antibiotic resistance underscores the urgent need for novel antibacterial agents. DNA gyrase, an essential enzyme involved in bacterial DNA replication, is a promising target for antibacterial therapy. Computational approaches offer a cost-effective means to design and screen potential inhibitors, such as eugenol derivatives. This study aims to computationally design eugenol derivatives as potential antibacterial agents targeting DNA gyrase, assess their binding affinities, evaluate physicochemical properties, and toxicity, and select lead compounds for further investigation. Molecular docking simulations were conducted to investigate the binding affinities of eugenol derivatives and controls to DNA gyrase. Physicochemical properties and toxicity assessments of eugenol were evaluated. Lead compounds were selected based on drug likeness, toxicity, and binding affinity. Molecular docking studies revealed varying binding affinities of eugenol derivatives to DNA gyrase, with lead compounds exhibiting superior affinity compared to eugenol. Physicochemical properties indicated moderate lipophilicity and low aqueous solubility for eugenol. Toxicity assessment revealed mutagenicity and tumorigenicity. De novo compound synthesis generated 244 novel compounds, with 44 selected based on drug-likeness, toxicity, and binding affinity as lead candidates. These findings provide valuable insights for the development of novel antibacterial agents targeting DNA gyrase, with implications for combating antibiotic resistance.

Skin infections considered as one of the predominant disorders that could greatly influence humans. Topical drug delivery is believed to be an effective substitute to systemically delivered medication for skin disorders management. Erythromycin has been proven to retain anti-bacterial activity. Based on that, the aim of existent study is to develop a proper nanocarrier, namely; nanoemulsion using tea tree oil including Erythromycin. Applying quality by design approach, the optimized nanoemulsion was selected based on number of independent variables namely; particle size and in vitro release study. Yet, in order to get appropriate topical application, the optimized nanoemulsion was combined with previously prepared hydrogel base to provide Erythromycin based nanoemulgel. The developed nanoemulgel was assessed for its organoleptic and physical characters to ensure its suitability for topical application. Stability study was implemented over three months after being kept in two distinct environments. Eventually, the antibacterial behavior of the preparation was investigated on MRSA to verify the expected antibacterial improvement and validate the effectiveness of the developed nanocarrier. The formulation showed consistent appearance, with pH (6.11 ± 0.19), viscosity (10400 ± 1275 cP), spreadability (54.03 ± 2.3 mm), extrudability (80.36 ± 3.15 g/cm2) and drug content (99.3 ± 0.46 %) that seemed to be satisfied for topical application. It could provide 48.1 ± 4.2 % releases over 6 h in addition to be stable at room temperature and at refrigerator. Ultimately, the formula showed a significant antibacterial activity against MRSA proving the combination and the nanocarrier effectiveness.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box–Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system.

Mupirocin is an antibacterial agent that has been documented to be effective in treating superficial skin infections. However, the main limitation of its application is bacterial resistance. Therefore, there is a need to determine a way to potentiate its efficiency. Accordingly, this obstacle led to this current investigation, which aims to find a way to improve the therapeutic action of mupirocin. This study focuses on the integration of tea tree oil with mupirocin to improve its antibacterial and wound healing capacities. Distinct nanoemulsions (NEs) were developed and the best of them were optimized using a central composite design (CCD) approach. The optimized NEs were mixed with a gel base to form a mupirocin-loaded nanoemulgel (NEG). The formulation was evaluated for characteristics including pH, viscosity, spreadability, and in vitro release over 6 h. The NEG was examined for its stability in two different conditions, namely at room temperature and refrigerated, for 3 months. Eventually, the NEG was inspected to determine its antibacterial and wound healing efficiencies. The developed mupirocin-loaded NEG exhibited good physical properties in terms of pH (6.13), viscosity (19,990 cP), spreadability (48.8 mm), and in vitro release over 6 h (51.4%). Moreover, it showed good stability with no significant difference in the evaluated parameters when stored for 3 months in the two conditions. Ultimately, mupirocin-loaded NEG prepared with tea tree oil exhibited a significant antibacterial influence in addition to good healing efficiency.

It is worthwhile to note that using natural products today has shown to be an effective strategy for attaining the therapeutic goal with the highest impact and the fewest drawbacks. In Saudi Arabia, date palm (Phoenix dactylifera) is considered the principal fruit owing to its abundance and incredible nutritional benefits in fighting various diseases. The main objective of the study is to exploit the natural products as well as the nanotechnology approach to obtain great benefits in managing disorders. The present investigation focused on using the powder form of date palm extract (DPE) of Khalas cultivar and incorporates it into a nanolipid formulation such as a nanostructured lipid carrier (NLC) prepared with palm oil. Using the quality by design (QbD) methodology, the most optimized formula was chosen based on the number of assigned parameters. For more appropriate topical application, the optimized DP-NLC was combined with a pre-formulated hydrogel base forming the DP-NLC-hydrogel. The developed DP-NLC-hydrogel was evaluated for various physical properties including pH, viscosity, spreadability, and extrudability. Additionally, the in vitro release of the formulation as well as its stability upon storage under two different conditions of room temperature and refrigerator were investigated. Eventually, different bacterial strains were utilized to test the antibacterial efficacy of the developed formulation. The optimized DP-NLC showed proper particle size (266.9 nm) and in vitro release 77.9%. The prepared DP-NLC-hydrogel showed acceptable physical properties for topical formulation, mainly, pH 6.05, viscosity 9410 cP, spreadability 57.6 mm, extrudability 84.5 (g/cm2), and in vitro release 42.4%. Following three months storage under two distinct conditions, the formula exhibited good stability. Finally, the antibacterial activity of the developed DP-NLC-hydrogel was evaluated and proved to be efficient against various bacterial strains.

Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways. Methods: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg). Results: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues. Conclusion: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.

The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (−17 to −26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient’s quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.

The present investigation aims to improve the antimicrobial influence of certain antibacterial drugs, namely, neomycin (NEO), exploiting the benefits of natural oils such as tea tree oil (TTO). Therefore, a distinctive nanolipid formulation, namely, a nanoemulsion (NE), was developed using a Central Composite Factorial Design (CCD) approach depending on the amount of TTO and tween 80 as surfactant. The optimized NEO-NE formula exhibiting minimum globular size and maximum in vitro release was selected. For efficient topical delivery, NEO-NE was incorporated into a pre-formulated hydrogel. The developed NEO-NE-hydrogel was characterized by its physical characteristics such as pH, viscosity, and spreadability. Next, it was tested for stability under different conditions for 3 months. Ultimately, an irritation test was conducted followed by an antibacterial examination. The preparation demonstrated acceptable properties to be successfully applied topically. It showed non-significant changes in stability in both conditions up to 3 months storage when compared to a fresh preparation. It exhibited no irritation when applied on hairless animal skin. Finally, TTO revealed a good inhibition for the bacterial growth that could improve the influence of NEO antibacterial activity, indicating the efficiency of NE containing NEO prepared with TTO to be a promising antibacterial nanocarrier.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (−1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.

The purpose of the present study was to explore the influence of a certain natural essential oil, namely eucalyptus oil, as an anti-inflammatory agent in addition to its prospective role in enhancing the action of meloxicam in reducing inflammation. As far as we know, this has been the first integration of meloxicam and eucalyptus essential oil into a nanoemulgel formulation intended for topical use. Primarily, eucalyptus oil was utilized in developing a nanoemulsion formulation incorporating meloxicam. A 22 factorial design was constructed using two independent variables (oil concentration and surfactant concentration) with two responses (particle size and % of in vitro release). One optimized formula was selected depending on the desirability function and subjected to a stability study. The optimized nanoemulsion was mixed with HPMC as a gelling agent to produce a meloxicam-loaded nanoemulgel, which was examined for its properties, stability, in vitro release and ex vivo permeation. Eventually, the anti-inflammatory activity was evaluated and compared with a placebo and corresponding gel formulation. The developed nanoemulgel revealed acceptable physical characteristics to be applied topically. Studying of the in vitro release was conducted successfully for 6 h. The ex vivo permeation from the nanoemulgel formulations was prompted, showing an appropriate value of the steady-state transdermal flux (SSTF). As a final point, the anti-inflammatory activity of the developed nanoemulgel revealed a valued anti-inflammatory influence. Additionally, the concurrence of eucalyptus essential oil and meloxicam was assured, and their potential in combating and lowering inflammation was supported.

Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box–Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.

One of the recent advancements in research is the application of natural products in developing newly effective formulations that have few drawbacks and that boost therapeutic effects. The goal of the current exploration is to investigate the effect of jojoba oil in augmenting the anti-inflammatory effect of Brucine natural alkaloid. This is first development of a formulation that applies Brucine and jojoba oil int a PEGylated liposomal emulgel proposed for topical application. Initially, various PEGylated Brucine liposomal formulations were fabricated using a thin-film hydration method. (22) Factorial design was assembled using two factors (egg Phosphatidylcholine and cholesterol concentrations) and three responses (particle size, encapsulation efficiency and in vitro release). The optimized formula was incorporated within jojoba oil emulgel. The PEGylated liposomal emulgel was inspected for its characteristics, in vitro, ex vivo and anti-inflammatory behaviors. Liposomal emulgel showed a pH of 6.63, a spreadability of 48.8 mm and a viscosity of 9310 cP. As much as 40.57% of Brucine was released after 6 h, and drug permeability exhibited a flux of 0.47 µg/cm2·h. Lastly, % of inflammation was lowered to 47.7, which was significant effect compared to other formulations. In conclusion, the anti-inflammatory influence of jojoba oil and Brucine was confirmed, supporting their integration into liposomal emulgel as a potential nanocarrier.

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF3-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF3 substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.

Date palm fruit (Phoenix dactylifera) is reputed to have numerous biological activities, including anticancer properties. To utilize the great fortune of this fruit, the current study aimed to maximize its pharmacological activity. Date palm extract (DPE) of Khalas cultivar was obtained in powder form and then was formulated into nanoemulsion (NE). The optimized DPE-NE was formulated along with its naked counterpart followed by studying their physical and chemical properties. A qualitative assessment of total serum protein associated with the surface of formulations was implemented. Studies for the in vitro release of DPE from developed NE before and after incubation with serum were investigated. Eventually, an MTT assay was conducted. Total phenolic and flavonoid contents were 22.89 ± 0.013 mg GAE/g of dry DPE and 9.90 ± 0.03 mg QE/g of dry DPE, respectively. Homogenous NE formulations were attained with appropriate particle size and viscosity that could be administered intravenously. The optimized PEGylated NE exhibited a proper particle size, PDI, and zeta potential. Total serum protein adsorbed on PEG-NE surface was significantly low. The release of the drug through in vitro study was effectively extended for 24 h. Ultimately; PEGylated NE of DPE attained significant inhibition for cancer cell viability with IC50 values of 18.6 ± 2.4 and 13.5 ± 1.8 µg/mL for MCF-7 and HepG2 cell lines, respectively. PEGylated NE of DPE of Khalas cultivar will open the gate for future adjuvants for cancer therapy.

In this study, we report the design, synthesis, computational and experimental evaluation of the antimicrobial activity, as well as docking studies of new 5-methylthiazole based thiazolidinones. All compounds demonstrated antibacterial efficacy, some of which (1, 4, 10 and 13) exhibited good activity against E. coli and B. cereus. The evaluation of antibacterial activity against three resistant strains, MRSA, P. aeruginosa and E. coli, revealed that compound 12 showed the best activity, higher than reference drugs ampicillin and streptomycin, which were inactive or exhibited only bacteriostatic activity against MRSA, respectively. Ten out of fifteen compounds demonstrated higher potency than reference drugs against a resistant strain of E. coli, which appeared to be the most sensitive species to our compounds. Compounds 8, 13 and 14 applied in a concentration equal to MIC reduced P. aeruginosa biofilm formation by more than 50%. All compounds displayed antifungal activity, with compound 10 being the most active. The majority of compounds showed better activity than ketoconazole against almost all fungal strains. In order to elucidate the mechanism of antibacterial and antifungal activities, molecular docking studies on E. coli Mur B and C. albicans CYP51 and dihydrofolate reductase were performed. Docking analysis of E. coli MurB indicated a probable involvement of MurB inhibition in the antibacterial mechanism of tested compounds while docking to 14α-lanosterol demethylase (CYP51) and tetrahydrofolate reductase of Candida albicans suggested that probable involvement of inhibition of CYP51 reductase in the antifungal activity of the compounds. Potential toxicity toward human cells is also reported.

The purpose of this study was to fabricate biostable inorganic silver nanoparticles (AgNPs) using fresh peel (aqueous) extract of Benincasa hispida. A fast, robust, and eco-friendly approach was used for the synthesis of AgNPs, where bioactive components of peel extract of B. hispida acted as reducing and stabilizing agents. Synthesized AgNPs were characterized using a UV–Vis spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and electron microscopy. The synthesized nanoparticles exhibited maximum absorption at 418 nm under the typical AgNPs surface plasmon resonance band range. They depicted a mean size of 26 ± 2 nm with a spherical shape. Their therapeutic prospective was determined by evaluating their antimicrobial and anticancer potential. The bio-synthesized silver nanoparticles exhibited strong antimicrobial activity with minimum inhibitory concentration (MIC 50) values of 14.5, 8.6, 6.063, and 13.4 μg/mL against Staphylococcus aureus (ATCC 25923), Micrococcus luteus (ATCC 14593), Escherichia coli (ATCC 25922), and Klebsiella pneumonia (ATCC 13883), respectively. The biosynthesized AgNPs showed potent in vitro cytotoxicity against human cervical cancer cell line with a half maximal inhibitory concentration (IC50) value of 0.066 μg/mL; however, no cytotoxic effect was observed on normal human primary osteoblasts cell line. This study explored B. hispida extract and confirmed its effectiveness as a promising source in producing AgNPs that could be employed for several therapeutic applications.

Transdermal delivery of insulin is a great challenge due to its poor permeability through the skin. The aim of the current investigation was to evaluate the prospective of insulin loaded niosome emulgel as a noninvasive delivery system for its transdermal therapy. A 23 full-factorial design was used to optimize the insulin niosome emulgel by assessing the effect of independent variables (concentration of paraffin oil, Tween 80 and sodium carboxymethyl cellulose) on dependent variables (in vitro release, viscosity and in vitro permeation). The physical characteristics of the prepared formulations were carried out by determining viscosity, particle size, entrapment efficiency, drug loading, drug release and kinetics. In vitro permeation studies were carried out using rat skin membrane. Hypoglycemic activity of prepared formulations was assessed in diabetic-induced rats. It was observed that the independent variables influenced the dependent variables. A significant difference (p < 0.05) in viscosity was noticed between the prepared gels, which in turn influenced the insulin release. The order of permeation is: insulin niosome emulgel > insulin niosome gel > insulin emulgel > insulin gel > insulin niosomes > insulin solution. The enhancement in transdermal flux in insulin niosome emulgel was 10-fold higher than the control (insulin solution). In vivo data significantly demonstrated reduction (p < 0.05) of plasma glucose level (at six hours) by insulin niosome emulgel than other formulations tested. The results suggest that the developed insulin niosome emulgel could be an efficient carrier for the transdermal delivery of insulin.